Ovarian cancer is the leading cause of cancer deaths in women worldwide and causes more deaths than all other gynecologic malignancies combined. All women are at risk for ovarian cancer, but older women are more likely to get the disease than younger women. About 90 percent of women who get ovarian cancer are older than 40 years of age, with the greatest number being 55 years or older. Although ovarian cancer remains the number one killer of women with gynecologic malignant hyperplasia, when ovarian cancer is found in its early stages, treatment is most effective. However, ovarian cancer does not cause many symptoms in its early stages. This is why most cases are not found until the cancer has spread. Ovarian cancer at its early stages (I/II) is difficult to diagnose; when it spreads and advances to later stages (III/IV), diagnosis is easier. This is due to the fact that most of the common symptoms are non-specific. Approximately 75% of women diagnosed with such cancer are already at the advanced stages (III and IV) of the disease at their initial diagnosis.
The serum BHCG level should be measured in any female in whom pregnancy is a possibility (Christoph Steinmeyer, Tumor Biol 2003; 24:13-22). Moreover, serum alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) should be measured in young girls and adolescents with suspected ovarian tumors because the younger the patient, the greater the likelihood of a malignant germ cell tumor. However, outside the aforementioned collection of substances, there has been a relative dearth of antigens which are useful in diagnosis and monitoring; this has been proven particularly true with respect to gynecologic malignancies, especially ovarian carcinomas, which frequently spread throughout the pelvic cavity before diagnosis of the condition. Many of these carcinomas typically exhibit a very aggressive growth pattern and generally respond well to chemotherapy. Thus, an accurate method by which early diagnosis of these diseases could be obtained is highly desirable.
A discovery (Bast, et al., N. Engl. J. Med. 309: 883 [1983]) of a serous cystadinocarcinoma ovarian antigen, known as CA125, has been found to be of significant value in monitoring patients with ovarian cancer. This antigen was isolated by using a monoclonal antibody, OC125, made by stimulation of mice with ovarian cancer cell line OVCA 433. It has been shown to recognize cell surface antigens of the OVCA 433 cell as well as 13 of 14 other ovarian cancer cell lines and a melanoma cell line. The antigen is a high molecular weight (>200,000 daltons) glycoprotein which has been partially purified from tissue culture medium (Masuko, et al., Cancer Res. 44: 2813, 1984). Furthermore, U.S. Pat. No. 4,921,790 relates to a 40 kilodalton subunit of serous cystadinocarcinoma ovarian tumor associated antigen CA125, useful in the diagnosis and monitoring of ovarian cancer. Although a blood test called CA-125 is useful in differential diagnosis and in follow-up on the disease, it has not been shown to be an effective method of screening for early-stage ovarian cancer due to its unacceptably low sensitivity and specificity. Elevated levels of serum CA125 alone or in combination with other known indicators, however, do not provide a definitive diagnosis of malignancy, or of a particular malignancy such as ovarian carcinoma.
Current research is looking at ways to combine tumor marker proteomics with other indicators of disease (i.e., radiology and/or symptoms) in order to improve accuracy. The challenge in such an approach is that the very low population prevalence of ovarian cancer means that even testing with very high sensitivity and specificity will still lead to a number of false positive results (i.e., performing surgical procedures in which cancer is not found). However, the contributions of proteomics are still in the early stages and require further refining. Current studies on proteomics mark the beginning of a paradigm shift towards individually tailored therapy. Currently, neither diagnosis nor five-year survival has greatly improved for these patients. This is substantially due to the high percentage of advanced-stage initial detection of the disease. Therefore, the challenge of developing new detection technology to improve early diagnosis and reduce the percentage of advanced-stage initial diagnoses still exists.